ArticleAnalytical chemistry2019
Imidazole Derivatives Improve Charge Reduction and Stabilization for Native Mass Spectrometry.
Article in Analytical chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Design of Fluorescent Membrane Scaffold Proteins for Nanodiscs.bioRxiv : the preprint server for biology · 2026Article
- Probing the Annular Lipid Belt of Membrane Proteins Using Native Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Hybrid Detergents Facilitate Scalable Charge Reduction and Stabilize Membrane Proteins While Retaining Lipid Interactions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Single particle charge detection mass spectrometry enables molecular characterization of lipid nanoparticles and mRNA packaging.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Design and Synthesis of Hetero-Bicephalic Detergents for Native Mass Spectrometry of Membrane Proteins.Journal of the American Chemical Society · 2025Article
- Electron Capture-Induced Charge Reduction Benefits the Recording of Ultralong Transients in Orbitrap-Based Individual-Ion Mass Spectrometry.Analytical chemistry · 2025Article
- Stabilization of Protein Interactions through Electrospray Additives in Negative Ion Mode Native Mass Spectrometry.Analytical chemistry · 2025Article
- Does Native Capillary Zone Electrophoresis-Mass Spectrometry Maintain the Structural Topology of Protein Complexes?Analytical chemistry · 2025Article
- The Role of Nanobubbles in Protein Unfolding during Electrothermal Supercharging.Journal of the American Society for Mass Spectrometry · 2025Article
- AsymmetricJournal of the American Chemical Society · 2024Article
- Native Mass Spectrometry of Membrane Protein-Lipid Interactions in Different Detergent Environments.Analytical chemistry · 2024Article
- Native mass spectrometry of membrane protein-lipid interactions in different detergent environments.bioRxiv : the preprint server for biology · 2024Article
- Structure and dynamics of endogenous cardiac troponin complex in human heart tissue captured by native nanoproteomics.Nature communications · 2023Article
- What's the defect? Using mass defects to study oligomerization of membrane proteins and peptides in nanodiscs with native mass spectrometry.Methods (San Diego, Calif.) · 2023Review
- Polyamine detergents tailored for native mass spectrometry studies of membrane proteins.Nature communications · 2023Article
- Emergence of mass spectrometry detergents for membrane proteomics.Analytical and bioanalytical chemistry · 2023Review
- Approaches to Heterogeneity in Native Mass Spectrometry.Chemical reviews · 2022Review
- Influenza AM2 Channel Oligomerization Is Sensitive to Its Chemical Environment.Analytical chemistry · 2021Article
- Lipid Head Group Adduction to Soluble Proteins Follows Gas-Phase Basicity Predictions: Dissociation Barriers and Charge Abstraction.International journal of mass spectrometry · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Noncovalent interactions between biomolecules are critical to their activity. Native mass spectrometry (MS) has enabled characterization of these interactions by preserving noncovalent assemblies for mass analysis, including protein-ligand and protein-protein complexes for a wide range of soluble and membrane proteins. Recent advances in native MS of lipoprotein nanodiscs have also allowed characterization of antimicrobial peptides and membrane proteins embedded in intact lipid bilayers. However, conventional native electrospray ionization (ESI) can disrupt labile interactions. To stabilize macromolecular complexes for native MS, charge reducing reagents can be added to the solution prior to ESI, such as triethylamine, trimethylamine oxide, and imidazole. Lowering the charge acquired during ESI reduces Coulombic repulsion that leads to dissociation, and charge reduction reagents may also lower the internal energy of the ions through evaporative cooling. Here, we tested a range of imidazole derivatives to discover improved charge reducing reagents and to determine how their chemical properties influence charge reduction efficacy. We measured their effects on a soluble protein complex, a membrane protein complex in detergent, and lipoprotein nanodiscs with and without embedded peptides, and used computational chemistry to understand the observed charge-reduction behavior. Together, our data revealed that hydrophobic substituents at the 2 position on imidazole can significantly improve both charge reduction and gas-phase stability over existing reagents. These new imidazole derivatives will be immediately beneficial for a range of native MS applications and provide chemical principles to guide development of novel charge reducing reagents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.